Advances in attenuating opioid-induced respiratory depression: A narrative review.

Opioids exert analgesic effects by agonizing opioid receptors and activating signaling pathways coupled to receptors such as G-protein and/or ß-arrestin. Concomitant respiratory depression (RD) is a common clinical problem, and improvement of RD is usually achieved with specific antagonists such as naloxone; however, naloxone antagonizes opioid analgesia and may produce more unknown adverse effects. In recent years, researchers have used various methods to isolate opioid receptor-mediated analgesia and RD, with the aim of preserving opioid analgesia while attenuating RD. At present, the focus is mainly on the development of new opioids with weak respiratory inhibition or the use of non-opioid drugs to stimulate breathing. This review reports recent advances in novel opioid agents, such as mixed opioid receptor agonists, peripheral selective opioid receptor agonists, opioid receptor splice variant agonists, biased opioid receptor agonists, and allosteric modulators of opioid receptors, as well as in non-opioid agents, such as AMPA receptor modulators, 5-hydroxytryptamine receptor agonists, phosphodiesterase-4 inhibitors, and nicotinic acetylcholine receptor agonists.

[The assessment of reliability and validity of musculoskeletal questionnaire].

OBJECTIVE: To evaluate the reliability and validity of musculoskeletal questionnaire. METHODS: A self-administered modified musculoskeletal questionnaire was used to investigate 12 098 workers from eight occupations, i.e. coal mining, petroleum, metallurgical, mechanical manufacturing, chemical, garment and railroad transportation industries and education. The Cronbach's α coefficient, analysis of covariance and multiple logistic regression were used to assess the reliability and validity of musculoskeletal questionnaire. RESULTS: The consistent test between total items of Musculoskeletal Questionnaire and each factor showed that the range of Cronbach's α was 0.52 ∼ 0.92, except from vibration factor, other Cronbach's α was more than 0.7. All 55 items of Musculoskeletal Questionnaire were subjected to factor analysis, and ten latent factors were identified, which explained 55.17% of the total variance. The potentially hazardous working conditions could be categorized into seven dimensions (force, dynamic load, static load, repetitive load, climate factors, vibration exposure and environmental ergonomic factor), which consisted with the theory model. The results of covariance analysis indicated that there were significant difference among 7 dimension indices in different jobs (P < 0.01). CONCLUSION: The modified Musculoskeletal Questionnaire is a valid and reliable tool for measuring musculoskeletal workload.

Influence of CYP3A5 and MDR1 genetic polymorphisms on urinary 6 beta-hydroxycortisol/cortisol ratio after grapefruit juice intake in healthy Chinese.

Interindividual variability of cytochrome P450 (CYP) 3A inhibition by grapefruit juice was investigated in relation to CYP3A5 and multidrug resistance gene (MDR) 1 genetic polymorphisms in Chinese Han, Uygur, and Kazakh healthy subjects. The measurement of urinary 6 beta-hydroxycortisol/cortisol ratio was used to evaluate CYP3A activity in vivo by high-performance liquid chromatography. CYP3A5*3 and MDR1 C1236T, G2677T/A, and C3435T polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism. After grapefruit juice intake, urinary ratios significantly decreased in 3 Chinese ethnic groups (P < .001). Kazakh had a larger decrease of urinary ratio compared to that of Han (P < .05), and the latter had similar decrease with Uygur. Furthermore, Chinese healthy subjects carrying CYP3A5*3/*3 and MDR1(1236-2677-3435) T-T-T/T-T-T genotypes were found to have the largest reduction of urinary ratio (mean, 61.4%; 95% confidence interval, 53.4%-69.5%), whereas *1/*3 subjects carrying MDR1(1236-2677-3435) C-G-C/C-G-C genotypes had the lowest reduction (mean, 25.9%; 95% confidence interval, 3.1%-48.8%; P < .01). In conclusion, both CYP3A5*3 and MDR1 variants influenced the extent of CYP3A inhibition by grapefruit juice in Chinese healthy subjects. The genetic variations influencing the CYP3A inhibitive phenotype might be helpful to explain the individual variability of grapefruit juice-drug interactions.

Frequencies of genotypes and alleles of the functional SNPs in CYP2C19 and CYP2E1 in mainland Chinese Kazakh, Uygur and Han populations.

CYP2C19 and CYP2E1 show great genetic differences between Orientals and Caucasians. The objective of this study was to investigate the genotype and allele distribution patterns of CYP2C19 and CYP2E1 polymorphisms among healthy participants in mainland Chinese Kazakh, Uygur and Han populations by the PCR-restriction fragment length polymorphism technique. The allele frequencies of CYP2C19 2, CYP2E1 5B and CYP2E1 6 were significantly lower in the Chinese Kazakh (15.4, 11.2 and 14.5%, respectively) (P<0.05) and Uygur (16.1, 12.1 and 18.8%) (P<0.05) populations than that in the Chinese Han population (28.8, 19.4 and 26.2%), but the frequencies of CYP2C19 3 were similar among the three populations (8.0, 9.4 and 7.2%). Frequencies of the three combined genotypes, one for predicted CYP2C19 poor metabolizers and two for predicted high levels of CYP2E1 transcription, were significantly lower in the Chinese Kazakh (7.5, 19.6 and 28.0%, respectively) (P<0.05, chi(2)-test) and Uygur (8.1, 22.8 and 33.6%) (P<0.05) populations compared with the Chinese Han population (16.5, 35.9 and 44.7%). The present research shows that frequencies of the functional single-nucleotide polymorphisms in the CYP2C19 and CYP2E1 genes vary in the Chinese Kazakh, Uygur and Han populations, suggesting that disease susceptibilities or drug responses associated with enzyme activities of CYP2C19 and CYP2E1 may differ in the diverse ethnic populations in mainland China.